Long-term Safety of Eplontersen Treated aTTR Patients and in Liver Transplant and Severely Hepatic Impaired Subpopulations

Overview

The aim of this observational cohort study is to characterise use of eplontersen in patients with prior liver transplant or with pre-existing severe hepatic impairment, as well as to assess long-term safety among all new users of eplontersen; all are areas of missing information Primary objectives are: 1. To describe demographic and clinical characteristics of patients at eplontersen initiation, including the prevalence of prior liver transplant (overall and by reason for liver transplant), and the prevalence of severe hepatic impairment; and to describe patients in these subgroups (prior liver transplant, severe hepatic impairment). 2. To describe long-term safety in patients who initiate eplontersen treatment, including onset of new clinical events, abnormal laboratory values and serious adverse events.

Study D8450R00003 enrolls adults (≥18 years) with a confirmed ATTR diagnosis at the time of informed consent. The sTTRing study will represent a subset of D8450R00003 participants who consent to secondary research use of their data and who initiated eplontersen treatment within 1 year prior to enrollment in D8450R00003. For comparative analyses, patients not exposed to eplontersen who initiated alternative ATTR therapies during the D8450R00003 observation period will also be included. sTTRing data collection will begin in Q3 2026 and conclude in Q1 2032. Interim analyses will be reported annually from Q3 2027 through Q3 2031, with a final report submitted in Q1 2033. The primary endpoints supporting the primary study objective are: (1) the prevalence of patients with a history of liver transplantation, categorized by reason for liver transplant, and (2) the prevalence of severe hepatic impairment. Safety outcomes will be summarized by incidence risk and event rates across prespecified time intervals (e.g., 0-6 months and from 7 months to the end of available follow-up) and over the full duration of follow-up. These summaries will be included in interim reports as part of both primary and secondary objectives. Cohort Event Monitoring will be used to identify safety events requiring further characterization. When more than 10 events are observed for a given outcome, cumulative hazard rates will be estimated. To optimize sample size, comparative analyses will be conducted, where feasible, at the final analysis and presented in the final report.